A pilot study on the rational use of medicines in four tertiary care hospitals through validated World Health Organization prescribing drugs indicators.

BACKGROUND: Appropriate utilization of therapeutic agents is a basic component of the quality of health outcomes for the patients and the community. A pilot study was conducted to evaluate the rational use of medicines and antibiotics, based on World Health Organization (who) prescribing indicators. STUDY DESIGN: We performed a retrospective, descriptive, cross-sectional pilot study in the medical outpatient departments in four tertiary care hospitals of Islamabad, Pakistan, in order to verify the correct prescribing of medicines according to the validated indicators prepared by the World Health Organization (who). METHODS: The Registries of all the prescriptions formulated during the period April 02 2017 - April 01 2018 by the outpatient departments of four tertiary care hospitals (two government funded hospitals (GH-A and GH-B) and two private funded hospitals (PH-C and PH-D) were considered. According to the World Health Organization recommendations, during the following month (April 02 2018 to May 1 2018), 600 prescriptions (150 per hospital) were collected by a random sampling method, verified and analyzed through a statistical tool (SPSS version 22.0). RESULTS: Mean number of medicines per prescription were 4.6 (Optimal value ≤ 2), with the highest value observed in GH-B hospital. Out of these, 350 (58.3%) (Optimal value < 30%) prescriptions consisted of antibiotics and 340 (56.6%) (Optimal value < 25%) prescriptions consisted of injectable medicines, with marked differences between hospitals. About 550 (19.6%) medicines were prescribed by generic name in all selected prescriptions with the lowest value observed in PH-D (9.9%) (Optimal value = 100%). Overall, 88% medicines were prescribed from National essential medicine list/formulary (Optimal value = 100%). All the prescribing core indicators showed significant difference between hospitals (P = 0.001). The most commonly prescribed antibiotic was ceftriaxone (37.4%), followed by ciprofloxacin (15.1%). CONCLUSIONS: Poor adherence to WHO prescribing indicators were observed in all medical outpatient departments in selected hospitals. WHO recommended core interventions should be implemented on trial basis to develop strategies to achieve long-lasting benefits.

Alterations of the thioredoxin system during subarachnoid hemorrhage-induced cerebral vasospasm.

BACKGROUND: The exact underlying pathogenic mechanisms and effective preventive or therapeutic interventions for cerebral vasospasm remain obscure. The thioredoxin (Trx) system performs important functions in the central nervous system including neurotrophic and neuroprotective actions. There is no study directly investigating the effects of subarachnoid hemorrhage (SAH) induced cerebral vasospasm on the Trx system in the literature. METHODS: Sixteen male New Zealand rabbits were randomly divided into two groups of eight rabbits each: a control group and a SAH group. The control group, (n = 8) was a sham surgery group in which SAH was not induced. In the SAH group, (n = 8), the SAH protocol was used to induce cerebral vasospasm. The brain and brainstem were removed and each brainstem was cut coronally into two pieces: an anterior part that contains basilar artery and a dorsal part that contains brainstem tissue. The brainstem tissue thioredoxin-1(Trx1), thioredoxin-2 (Trx2), thioredoxin reductase (TrxR), thioredoxin reductase-1 (TrxR1), thioredoxin-interacting protein (TXNIP) levels were investigated. Total oxidant status (TOS), total antioxidant status (TAS), malondialdehyde levels (MDA) and tumor necrosis factor alpha (TNF-alpha) levels were investigated for determining the oxidative-antioxidative status of the related brain tissues. Basilar artery segments were investigated for cross-sectional area and wall thickness measurements. RESULTS: SAH statistically significantly reduced the tissue levels of Trx1 (p < 0.01) and TrxR (p < 0.01). Trx2 levels were not significantly altered after SAH (p > 0.05). SAH significantly reduced the expression of TrxR1 (p < 0.01) and significantly increased the expression of TXNIP (p < 0.01) when compared with controls. TOS levels and MDA levels significantly increased after SAH (p < 0.01) and TAS levels significantly reduced after SAH (p < 0.01). TNF-alpha levels significantly increased after SAH (p < 0.01). SAH-induced cerebral vasospasm significantly (p < 0.05) increased the wall thickness and reduced the mean cross-sectional area of the basilar artery (p < 0.05). CONCLUSIONS: The Trx system seems to be negatively affected by the simultaneously interrelated enzymatic alterations during cerebral vasospasm.

Congenital cervical dermal sinus tract caused tethered cord syndrome in an adult: a case report.

The objective of this study was to report on a 34-year-old woman who presented with tethered cord syndrome due to dermal sinüs tract. A 34-year-old woman had got dermal sinüs tract admitted to our hospital with swelling on the neck, pain and numbness on the left upper limb. She was treated by surgical removal of dermal sinuses and untethering the spinal cord which is stretched by the dermal sinus. Congenital dermal sinus tracts are uncommon types of cranial and spinal dysraphisms. They can occur in the midline of the craniospinal axis from the occiput to the sacral region. For dermal sinuses, cervical region is very rare location that is reported in the literature. They are diagnosed usually in childhood with skin signs, neurological deficits, local infections and meningitis. We present a rare case of dermal sinus tract located in cervical region. Early diagnosis and treatment of cervical dermal sinus tract are important to prevent neurological deficits.

Synthesis and modeling of polysiloxane-based salt-in-polymer electrolytes with various additives.

The effect of both nanoparticles and low molecular weight borate esters on the ionic conductivity of cross-linked polysiloxanes was systematically investigated by means of measuring conductivity spectra in the impedance regime at temperatures between -30 and 90 degrees C. Salt-in-polymer electrolytes were prepared by dissolving lithium triflate (LiSO(3)CF(3)) in comblike polysiloxanes bearing one methyl and one oligoether side group per silicon. An amount of 10 mol % of the oligoether side groups exhibited a terminal allytrimethoxysilane serving as a cross-linker moiety (T(0.1)OPS). Thus prepared polymer electrolyte membranes were completely amorphous and mechanically stable with an optimum conductivity value of 5.7 x 10(-5) S x cm(-1) at 15 wt % of lithium triflate (LiSO(3)CF(3)) at room temperature (T(0.1)OPS + 15 wt % LiSO(3)CF(3)). Further investigations concerned the influence of additives, i.e., nanosized ceramic fillers (alpha-Al(2)O(3) and SiO(2), up to 10 wt %) as well as two low molecular weight borate esters (tris(2-(2-methoxyethoxy)ethyl) borate (B2) and tris(2-(2-(2-methoxyethoxy)ethoxy)ethyl) borate (B3)) with maximum concentrations of 40 wt % as referred to polysiloxane T(0.1)OPS. The addition of borate esters resulted in a considerable increase of the conductivity, while still maintaining the mechanical stability. Optimum conductivities of 3.7 x 10(-5) and 1.6 x 10(-4) S x cm(-1) were measured for B2 and B3, respectively, at room temperature. A fit of the temperature-dependent DC conductivity by the empirical Vogel-Tammann-Fulcher (VTF) equation showed that there was an increased number density of mobile charge carriers in the case of borate esters as additives. However, the shape of the conductivity spectra in the dispersive regime changed considerably in going from nanoparticles as additives to borate esters. A careful and consistent modeling of the conductivity spectra and of the temperature dependence of the DC conductivity was done within the framework of the MIGRATION concept. The result was that the addition of borate esters to the polymer host most probably increased both number density of mobile charge carriers as well as their mobility.

Inhibitory actions of hydroxocobalamin, cyanocobalamin, and folic acid on the ultraviolet light-induced relaxation of the frog upper oesophageal strip.

The applications of ultraviolet (UV) light (336 nm) on the upper oesophageal strips of frog elicited relaxant responses in the presence of NaNO2 (50 microM). The tissues were mounted under the tension 0.5 g in an organ bath containing Ringer solution, maintained at 25 degrees C and gassed with 100% O2. The responses were recorded on a kymograph via an isotonic lever. Antimegaloblastic agents, including hydroxocobalamin (1, 10, and 100 microM), cyanocobalamin (1, 10, 25, and 100 microM), and folic acid (1, 10, 50, 100, and 200 microM), significantly attenuated the relaxation response to UV light. Folinic acid (1, 10, 25, and 100 microM), however, enhanced the relaxation. Pyrogallol (50 microM), hydroquinone (50 microM), and diethyldithiocarbamic acid (8 mM) were found ineffective for attenuation, though FeSO4 (200, 400, and 500 microM) and hemoglobin (50 microM), respectively, exerted significant inhibition. L-arginine methylester (500 microM) did not impair UV-induced relaxation. Based on these results, we concluded that a mechanism involving undefined action(s) of antimegaloblastic drugs may cause alterations in the UV light-induced relaxation of the tissue used.

Possible postsynaptic action of aminoglycosides in the frog rectus abdominis.

The present study was undertaken to investigate the postsynaptic effects of aminoglycosides on contractions evoked by acetylcholine (ACh), KCl, electrical field stimulation (EFS) and Na(+)- and Ca(2+)-free Ringer solution with 0.2 mM Na2 EDTA (NaFCaFR) in the isolated frog rectus abdominis. Neomycin inhibited contraction elicited by ACh, NaFCaFR, and EFS at the higher frequencies (8 and 10 Hz) but not those elicited by KCl and EFS at the lower frequencies (2, 3 and 5 Hz). D-tubocurarine inhibited ACh-induced contractions in a concentration-dependent manner. In addition, drug reduced EFS-evoked contractions to a limited extent. Lower concentrations (10(-5), 5 x 10(-5), 10(-4), 2 x 10(-4) and 3 x 10(-4) M) but not higher concentrations (4 x 10(-4) and 5 x 10(-4) M) of methoxyverapamil exhibited a concentration-dependent inhibitory action on NaFCaFR-induced contractions. Similar inhibitions of the same type of contraction were displayed by aminoglycosides (neomycin, streptomycin, netilmycin, gentamycin and amikacin). These results suggest that in addition to their antagonistic action on nicotinic receptors in the frog rectus abdominis, aminoglycosides may exert stabilizing effects on some functional components contributing to contractions at the membrane.

Evidence that the nitrergic neurotransmitter and endothelium-derived relaxing factor might be S-nitrosothiols in the mouse corpus cavernosum.

The effects of thimerosal, a sulfhydryl oxidizing agent on nitrergic, endothelium-dependent and -independent relaxations were investigated to examine the possibility that the nitrergic neurotransmitter and endothelium-derived relaxing factor (EDRF) could be S-nitrosothiol or free nitric oxide (NO) in the isolated mouse corpus cavernosum. Thimerosal (5 x 10(-6)-2 x 10(-5) M) inhibited or almost abolished electrical field stimulation--(EFS, 30V, 0.5 ms, 15 sec, 1, 2, 4, 8, 16 Hz), acetylcholine--(ACh, 5 x 10(-8)-1.25 x 10(-6) M), glyceryl trinitrate--(GTN, 3 x 10(-7)-3 x 10(-6) M), and S-nitrosoglutathione--(GSNO, 5 x 10(-6)-1.25 x 10(-4) M) induced relaxations. Thiomerosal inhibition seems to be specific to L-arginine NO pathways since it had no effect on acidified sodium nitrite--(10(-4)-5 x 10(-4) M), photoactivated sodium nitrite--(2 x 10(-4) M), isoprenaline--(10(-6) M), or papaverine--(10(-4) M) elicited relaxations. Moreover, the inhibitory effect of thimerosal on the nitrergic, ACh- or GTN-induced relaxations were partly reversed by sulfhydryl-containing compounds, L-cysteine (10(-3) M), dithiothreitol (10(-3) M), or glutathione (10(-3) M). However L-methionine (10(-3) M), which contains a methyl group on the sulphur atom, failed to restore the thimerosal inhibition. Thimerosal did not change the contraction produced by 10(-4) M NG-nitro-L-arginine methyl ester. These findings indicate that the nitrergic neurotransmitter as well as EDRF may not be free NO but NO-transferring molecules, probably S-nitrosothiols, in the mouse corpus cavernosum.

A possible role of S-nitrosothiols at the nitrergic relaxations in the mouse corpus cavernosum.

Relaxations induced by electrical field stimulation and acetylcholine were compared with those induced by acidified sodium nitrite, sodium nitroprusside, S-nitrosoglutathione and S-nitroso-N-acetyl-D,L-penicillamine in the mouse corpus cavernosum precontracted with phenylephrine. NG-nitro-L-arginine inhibited electrical field stimulation- or acetylcholine-induced relaxation, but was ineffective on relaxations caused by the other stimuli. Hydroquinone and pyrogallol had no inhibitory action on the relaxations caused by any stimulus except acidified sodium nitrite. Incubation of the tissue with diethyldithiocarbamic acid significantly inhibited the relaxations induced by all stimuli except papaverine. In the tissues pre-treated with diethyldithiocarbamic acid, superoxide dismutase, hydroquinone and pyrogallol failed to yield restore or further inhibit the relaxations in response to electrical field stimulation or acetylcholine. LY 83583 (6-anilino-5,8-quinolinedione) and hydroxocobalamin clearly inhibited the relaxant responses to electrical field stimulation, acetylcholine, S-nitrosoglutathione and acidified sodium nitrite whereas there was significant enhancement of the relaxation produced by S-nitroso-N-acetyl-D,L-penicillamine. These findings suggest that the relaxant factor released from non-adrenergic non-cholinergic nerves or endothelial cells in mouse cavernosal tissue may be a superoxide anion-resistant nitric oxide-containing molecule and that S-nitrosoglutathione rather than S-nitroso-N-acetyl-D,L-penicillamine could be a suitable candidate for this.

The effect of Ba2+ on the nitrergic mechanism in the isolated frog lung preparation.

1. The present study was undertaken to investigate effects of Ba2+ on the isolated frog lung strips depolarized by 20 mM K+ in Ca2+ free Ringer solution. 2. Ba2+ produced monophasic relaxant response, whereas Ca2+ induced biphasic response consisting of a transient relaxation and a marked contraction. Both kinds of relaxation were inhibited completely by L-NOARG. L-arginine reversed the action of L-NOARG. 3. Ferrous sulfate, pyrogallol, hydroquinone, and vanadate reduced the Ba(2+)-induced relaxation in a concentration-dependent manner. 4. These findings suggest that Ba(+)-induced relaxation may fully be mediated by the nitrergic mechanism and the effect of Ba2+ on the nitric oxide synthase may be more selective than Ca2+.

The role of Na+ channels in twitch generation during exposure of the frog rectus abdominis to Ca-free Ringer solution with Na2EDTA.

The aim of the study was to investigate whether Na+ channels play a role in the twitch component of the response of the isolated frog rectus abdominis to Ca(2+)-free Ringer solution with 0.2 mM Na2EDTA by using tetrodotoxin and some other well known drugs that exhibit a blocking action on Na+ channels. In the presence of 5 x 10(-7) M tetrodotoxin, the twitch component, measured isotonically, disappeared. Although 10(-7) M d-tubocurarine was found to be ineffective, a complete blockage of twitch amplitude was observed at 5 x 10(-6) M concentration of the drug. The inhibitory action of d-tubocurarine on twitch response was not antagonized by 10(-6) and 10(-5) M carbachol. Propranolol (10(-6) - 10(-5) M), lidocaine (2 x 10(-6) - 10(-5) M), quinine (10(-6) - 2 x 10(-5) M) and quinidine (10(-6) - 2 x 10(-5) M) inhibited maximal twitch amplitude in a concentration dependent manner. These findings strongly suggest that activation of tetrodotoxin sensitive Na+ channel may play a primary role at twitch generation during exposure of the frog rectus abdominis to Ca(2+)-free Ringer solution with Na2 EDTA.

Distinction of structural reorganisation and ligand binding in the T<==>R transition of insulin on the basis of allosteric models.

Two allosteric models are presented for the T<==>R transition of insulin hexamers in the presence of phenolic ligands which are based on existing experimental information. The transition mainly involves residues 1-8 of the B-chain, i.e. 15% of the molecule, which are extended in the T- and helical in the R-state. The main facts to be accounted for are: 1) the transition is undergone trimer-wise; 2) the transition of the second trimer is disadvantaged compared to the first one; 3) the subunits of a trimer undergo transition in a cooperative process; 4) binding sites for phenolic ligands only exist in R3 trimers; 5) ligands shift the equilibrium by arresting the R-state; 6) the ligand is accommodated in a pocket made up between two adjacent subunits; 7) binding one ligand molecule extends the lifetime of the two other binding sites of a trimer; 8) only ligand-free trimers can undergo transitions. The two models allowed for CD spectroscopic titrations of zinc and cobalt insulin with phenol and m-cresol to be assessed in terms of structural reorganisation and ligand binding, and for the respective standard free energy differences to be calculated. delta G degrees for the reorganisation of the first timer in zinc-insulin is about 8 kJ/mol, and for that of the second trimer, 21kJ/mol. The corresponding values for cobalt-insulin are 12 and 24 kJ/mol, respectively. For both zinc- and cobalt-insulin, the delta G degrees for phenol and m-cresol binding is about -18 kJ/mol. Both models are equally compatible with the titration data.

Kinetic measurements of T----R structural transitions in insulin.

The T6----T3R3 and T3R3----R6-structural transitions of cobalt insulin hexamers as induced by SCN ions or m-cresol were studied in stopped-flow experiments using the absorption in the visible for monitoring their time course. The T6----T3R3 transition induced by either SCN or limited concentrations of m-cresol is mono-exponential with a rate constant of 0.1 s-1 and 0.4 s-1, respectively. A mono-exponential time course is also encountered for the m-cresol-induced T3R3----R6 transition when starting from the T3R3 state preestablished by either SCN or m-cresol. The corresponding rate constants are 1.3 s-1 and 0.49 s-1, respectively. If m-cresol is used beyond the concentration range where transformation is limited to one trimer, two exponentials are required for fitting the time course. The second exponential corresponds to the T3R3----R6 step with a concentration-independent rate constant of 0.4 s-1. The rate constant for the faster T6----T3R3 transition, however, increases with increasing excess of m-cresol.